Editorial comment on: Cizolirtine Citrate is safe and effective for treating Urinary Incontinence secondary to overactive bladder: a Phase 2 proof-of-concept study

Overactive bladder (OAB) has high prevalence in women and men and has a significant negative impact on quality of life as well as growing costs for treatment [1,2]. Antimuscarinics are used as first-line drug therapy for OAB. Currently, a considerable number of antimuscarinic drugs are on the market. Moreover, dose flexibility and different drug formulations improve the efficacy of antimuscarinic agents [3]. Patient compliance and treatment persistence, however, are still insufficient in clinical practice [4]. Recent neuropharmacologic developments in the understanding of the micturition reflex have led to new alternative therapeutic modalities for OAB. The present paper by Za´ t’ura and coworkers reports the safety and effectiveness of a new agent in the treatment of OABwith urinary incontinence [5]. The study was designed as a multicenter, randomized, double-blind phase 2 protocol. The primary objective was to prove the clinical efficacy of cizolirtine citrate, an inhibitor of substance P and calcitonine gene-related peptide release at the spinal-cord level, comparedwith placebo. In the previous pilot study of 79 symptomatic patients with urinary incontinence secondary to OAB, the authors showed evidence of therapeutic efficacy and good tolerability of cizolirtine citrate using two dosages: 200 mg twice a day (bid) and 400 mg bid [6]. The present trial of 135 patients confirms the results of the pilot study, showing a significant reduction of the total number of voidings per 24 h. Moreover, the authors conclude that cizolirtine citrate (400 mg bid) may be suitable as a complementary or alternative agent to antimuscarinics in the treatment of OAB. Adverse events caused by cizolirtine citrate were similar to those caused by anticholinergics, with predominantly gastrointestinal and neurologic symptoms. Further research with more detailed objective assessment of OAB symptoms as well as patient group definitions are needed to prove the efficacy and safety of cizolirtine citrate. Phase 3 studies related to the comparability of this promising new agent and the antimuscarincs are necessary.